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酒精诱导的氧化应激与突触体膜特性之间的关联:维生素E的保护作用。

Association between alcohol-induced oxidative stress and membrane properties in synaptosomes: A protective role of vitamin E.

作者信息

Reddy Vaddi Damodara, Padmavathi Pannuru, Bulle Saradamma, Hebbani Ananda Vardhan, Marthadu Shakeela Begum, Venugopalacharyulu N Ch, Maturu Paramahamsa, Varadacharyulu N C

机构信息

Department of Biochemistry, Sri Krishnadevaraya University, Anantapur 515 003, AP, India..

Oil Technological Research Institute, Jawaharlal Nehru Technological University Anantapur, Anantapuramu 515001, India.

出版信息

Neurotoxicol Teratol. 2017 Sep;63:60-65. doi: 10.1016/j.ntt.2017.07.004. Epub 2017 Aug 1.

Abstract

Chronic and excessive alcohol consumption leads to various neurological diseases. Synaptosomes are ideal organelles to study the functional properties of the brain in alcoholism. This study focuses on the association between oxidative stress and synaptosomal membrane properties in alcohol treated rats. Sixty day old male albino rats were treated with 20% alcohol at 5g/kg body weight/ day for sixty days. Alcohol administration significantly increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyls with decreased catalase, glutathione peroxidase (GPx), superoxide dismutase (SOD) activities and reduced glutathione (GSH) content in synaptosomes. Further, alcohol administration decreased (cholesterol/phospholipids) C/P ratio in synaptosomal membranes, which was further confirmed using 1,6 diphenyl 1,3 hexatriene (DPH) as fluorescent probe. Moreover, alcohol treatment also increased membrane bound Na/K-ATPase, Ca-ATPase and Mg-ATPase enzyme activities. Correlation (r) analysis revealed that anisotropic (γ) values were strongly associated with lipid peroxidation (r=0.678) and Na/K-ATPase activity (r=0.793). The results of the present study clearly indicate that lipid peroxidation was positively correlated (r=0.621) with Na/K-ATPase activity and C/P ratio was negatively associated (r=-0.549) in alcohol treated animals. Similar results were found on alcohol treatment (50 and 100mM) of brain synaptosomes in vitro. But with the co-treatment of vitamin E reversed these changes. In conclusion, synaptosomal membranes properties are impaired due to increased oxidative stress, changes in lipid composition, altered fluidity and membrane bound enzyme activities. And treatment with vitamin E renders protection against ethanol-induced membrane alterations.

摘要

长期过量饮酒会导致多种神经疾病。突触体是研究酒精中毒时大脑功能特性的理想细胞器。本研究聚焦于酒精处理大鼠中氧化应激与突触体膜特性之间的关联。60日龄雄性白化大鼠每天按5克/千克体重给予20%酒精,持续60天。给予酒精显著增加了硫代巴比妥酸反应性物质(TBARS)和蛋白质羰基水平,同时突触体中过氧化氢酶、谷胱甘肽过氧化物酶(GPx)、超氧化物歧化酶(SOD)活性降低,谷胱甘肽(GSH)含量减少。此外,给予酒精降低了突触体膜中的(胆固醇/磷脂)C/P比值,这使用1,6 - 二苯基 - 1,3 - 己三烯(DPH)作为荧光探针得到了进一步证实。而且,酒精处理还增加了膜结合的钠钾 - ATP酶、钙 - ATP酶和镁 - ATP酶的活性。相关性(r)分析表明各向异性(γ)值与脂质过氧化(r = 0.678)和钠钾 - ATP酶活性(r = 0.793)密切相关。本研究结果清楚地表明,在酒精处理的动物中,脂质过氧化与钠钾 - ATP酶活性呈正相关(r = 0.621),C/P比值呈负相关(r = -0.549)。在体外对脑突触体进行酒精处理(50和100mM)时也发现了类似结果。但维生素E的共同处理逆转了这些变化。总之,由于氧化应激增加、脂质组成改变、流动性改变和膜结合酶活性变化,突触体膜特性受损。而维生素E处理可防止乙醇诱导的膜改变。

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